This blog began in 2007, focusing on anthrax vaccine, and later expanded to other public health and political issues. The blog links to media reports, medical literature, official documents and other materials.

In order to produce polyvalent vaccines based on single rVSV vector, we investigated the immunogenicity, antibody neutralizing activity, and antigenic determinant domain of Zaire Ebola's fragment MFL (aa 393-556) that contains furin site and internal fusion loop. Both the recombinant protein and the recombinant plasmid of fragment MFL elicited high levels of antibody, similar to those of Zaire Ebola GP (ZGP). The MFL fragment of ZGP also elicited high levels of neutralizing antibody and induced moderate cellular immune response in mice, as revealed by the proliferation and cytokine secretion of splenocytes. Through the analysis of the induction of neutralizing antibody by pVAX1-based recombinant plasmids that expressed truncated fragments of MFL, we found that the domain containing the internal fusion loop and the furin site was the major contributor of fragment MFL's immunogenicity. Furthermore, the rVSV-based bivalent vaccine expressing Sudan Ebola GP (SGP) and MFL fragment elicited efficient cross-immunity against ZGP and SGP with high levels of neutralizing antibody. Our results indicate that fragment MFL is an effective and novel antigen for the production of neutralizing antibody and polyvalent vaccines of Ebola virus.

Infectious disease has only recently been recognized as a major threat to the survival of Endangered chimpanzees and Critically Endangered gorillas in the wild. One potentially powerful tool, vaccination, has not been deployed in fighting this disease threat, in good part because of fears about vaccine safety. Here we report on what is, to our knowledge, the first trial in which captive chimpanzees were used to test a vaccine intended for use on wild apes rather than humans. We tested a virus-like particle vaccine against Ebola virus, a leading source of death in wild gorillas and chimpanzees. The vaccine was safe and immunogenic. Captive trials of other vaccines and of methods for vaccine delivery hold great potential as weapons in the fight against wild ape extinction.

Antigen presenting cells (APCs), including macrophages and dendritic cells, are early and sustained targets ofEbola virus (EBOV) infection in vivo. Because EBOV activates mitogen-activated protein kinase (MAPK) signaling upon infection of APCs, we evaluated the effect of pyridinyl imidazole inhibitors of p38 MAPK on EBOV infection of human APCs and EBOV mediated cytokine production from human DCs. The p38 MAPK inhibitors reduced viral replication in PMA-differentiated macrophage-like human THP-1 cells with an IC50 of 4.73μM (SB202190), 8.26μM (p38kinhIII) and 8.21μM (SB203580) and primary human monocyte-derived dendritic cells (MDDCs) with an IC50 of 2.67μM (SB202190). Furthermore, cytokine production from EBOV-treated MDDCs was inhibited in a dose-dependent manner. A control pyridinyl imidazole compound failed to inhibit either EBOV infection or cytokine induction. Using an established EBOV virus-like particle (VLP) entry assay, we demonstrate that inhibitor pretreatment blocked VLP entry suggesting that the inhibitors blocked infection and replication at least in part by blocking EBOV entry. Taken together, our results indicate that pyridinyl imidazole p38 MAPK inhibitors may serve as leads for the development of therapeutics to treat EBOV infection.

Filovirus infections cause fatal hemorrhagic fever
characterized by the initial onset of general symptoms before rapid progression
to severe disease; the most virulent species can cause death to susceptible
hosts within 10 days after the appearance of symptoms. Before the advent of
monoclonal antibody (mAb) therapy, infection of nonhuman primates (NHPs) with
the most virulent filovirus species was fatal if interventions were not
administered within minutes. A novel nucleoside analogue, BCX4430, has since
been shown to also demonstrate protective efficacy with a delayed treatment
start. This review summarizes and evaluates the potential of current
experimental candidates for treating filovirus disease with regard to their
feasibility and use in the clinic, and assesses the most promising strategies
towards the future development of a pan-filovirus medical countermeasure.J Antimicrob Chemother. 2014 Aug;69(8):2123-31. doi: 10.1093/jac/dku091. Epub 2014 Apr 7.

Filoviruses such as Ebola virus and Marburg virus cause a severe haemorrhagic fever syndrome in humans for which there is no specific treatment. Since filoviruses use a complex route of cell entry that depends on numerous cellular factors, we hypothesized that there may be drugs already approved for human use for other indications that interfere with signal transduction or other cellular processes required for their entry and hence have anti-filoviral properties.

METHODS:

We used authentic filoviruses and lentiviral particles pseudotyped with filoviral glycoproteins to identify and characterize such compounds.

RESULTS:

We discovered that amiodarone, a multi-ion channel inhibitor and adrenoceptor antagonist, is a potent inhibitor of filovirus cell entry at concentrations that are routinely reached in human serum during anti-arrhythmic therapy. A similar effect was observed with the amiodarone-related agent dronedarone and the L-type calcium channel blocker verapamil. Inhibition by amiodarone was concentration dependent and similarly affected pseudoviruses as well as authentic filoviruses. Inhibition of filovirus entry was observed with most but not all cell types tested and was accentuated by the pre-treatment of cells, indicating a host cell-directed mechanism of action. The New World arenavirus Guanarito was also inhibited by amiodarone while the Old World arenavirus Lassa and members of the Rhabdoviridae (vesicular stomatitis virus) and Bunyaviridae (Hantaan) families were largely resistant.

After swimming with dolphins at Key Largo, they checked me out at the edge of the pool

Visiting a Bhutanese Dzong, the regional seat of both government and religion (and a fort for good measure)

Why am I blogging?

Because life is meant to be lived! The left side of this blog has photos of some peak experiences. And the right side contains information about which I am passionate.

Too many peoples' lives are characterized by lack of authenticity, and fear of acknowledging and expressing their true nature. Employees cannot say what they think at work, and in the corporate system we must squish ourselves into square holes when we are round pegs. We thus lose touch with our souls, becoming cogs in a soulless, profit-driven machine.

The culture of political correctness has meant, in medicine, that we ignore how the foundations of our science are being undermined by commercialism. Clinical data generated or presented by the manufacturers of drugs, vaccines and devices cannot be trusted: there are hundreds of studies proving this. But this fraudulent information continues to be the only data informing the approval and use of vaccines, drugs and devices.

Unless scrupulous ethical conduct is demanded of physicians and biological scientists, our lack of meaningful standards will carry the medical-pharmaceutical system down the path of increasing irrelevance.

Medicine and its tools need to be affordable. The current medical-industrial milieu, characterized by contempt for science, countless ways for insiders to achieve wealth due to failure of good governance, and regulatory agency-to-industry revolving doors, has ushered in stratospheric pricing... further kicking us down that path to irrelevance.

Why is our new health care plan a giveaway to health industries instead of to health consumers? Wha won't it cover all Americans? Why was the "public option" never an option for the Obama administration?

So many of our leaders carry a heavy burden of mendacity and avarice. If they instead got in touch with their own souls (perhaps by exposure to the natural world), or made their decisions by maximizing the amount of good that results, our leaders might find real meaning and value in their lives.

Until that happens, the only way to straighten out the current mess is to demand accountability and impose penalties on unethical/dishonest leaders. Both political parties enjoy bounteous hors d'oeuvres from Pharma's table, making it unlikely the existing political "process" will provide relief--as we've seen in the demoralizing healthcare reform drama.

Until then, I'll continue to "call it as I see it" in this blog -- working and living the way life should be, in rural Maine, far from the centers of power.

Ellen Byrne has created several designs encapsulating aspects of the FBI's ridiculous case against Bruce Ivins. They can be purchased on T-shirts and coffee mugs. All proceeds will be donated to the the Frederick County chapter of the American Red Cross, a favored charity of Dr. Bruce Ivins.